Principal Investigator
Professor for cellular and molecular Physiology
Our lab integrates molecular, genetic and cell biology approaches with live cell imaging and in vivo neuroanatomy techniques to understand the role of membrane trafficking and autophagy in the pathogenesis of age-dependent neurodegenerative diseases.
The dysfunction of autophagy in the brain is accompanied by the accumulation of insoluble protein inclusions, but the prevention of inclusion formation does not suppress neurodegeneration in autophagy-deficient mice. This challenges the doctrine of protein aggregate removal as a sole function of neuronal autophagy and raises the question: “What is the precise physiological role of autophagy in the brain”? Our lab is uniquely positioned to explore this question by integrating state-of-the-art genetic and cell biology approaches with live-cell imaging and neuroanatomy. Using this multidisciplinary approach, we discovered that autophagy functions in the brain to regulate axonal microtubule dynamics independently of its role in protein degradation. We found that autophagy proteins, which are crucial for autophagosome expansion, also mediate the intracellular cargo transport in neurons and are important regulators of neuronal-activity dependent gene expression. How autophagy proteins switch from their canonical function in protein degradation to cargo transport regulation is currently unknown. We believe that our studies could revolutionize our understanding of molecular mechanisms of neurodegeneration.
Increased induction of autophagy is relatively frequent in neurodegenerative diseases. While increased autophagy has been shown to facilitate the clearance of aggregation-prone proteins and promote neuronal survival, growing evidence indicate that too much autophagic activity can be detrimental and lead to neuronal death. The long-term goal of Dr. Kononenko’s lab is to understand the role of autophagy in the pathology of neurodegenerative diseases. To reveal the role of autophagy in the brain areas selectively vulnerable to neurodegeneration, the group of Dr. Natalia Kononenko aims to develop mouse models for monitoring autophagic turnover rates in the brain in vivo. Given the therapeutic potential of autophagy modulation in neurodegenerative disease, the research performed by Dr. Kononenko’s group may provide new therapeutic targets for treatment of age-associated neurodegenerative disorders.
“The reward of the scientist is the emotional thrill of being the first person in the history of the world to see something or to understand something. Nothing can compare with that experience” – Cecilia Payne-Gaposchkin
Dr. Natalia Kononenko and her co-workers have contributed to the understanding of the molecular and cell biological regulation of autophagosomal trafficking in neurons. The group has identified the endocytic adaptor protein complex-2 (AP-2) as a novel adaptor for autophagosomal trafficking in neurons (Bera et al., 2020) and discovered the role in regulation of microtubule dynamics (Negrete-Hurtado et al., 2020) and synaptic PKA signaling (Overhoff et al., 2022).
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Principal Investigator
Professor for cellular and molecular Physiology